Mechanisms of selective cytotoxicity of adriamycin (Am) and daunomycin (Dm; rubimycin, daunorubicin) and other agents will be investigated in tumor cells and in animals. Am and Dm have been selected as model agents for comparative purposes. Both are similarly acting anthracycline aminoglycosidic anticancer antibiotics with established, although contrasting, therapeutic value in the treatment of human neoplasias. The objectives of the proposed study are: 1) to describe their actions on DNA as possible contributory factors to long- term toxicity and differential therapeutic actions; and 2) to establish the cellular basis for the selective cytotoxicity which contributes to the therapeutic superiority of Am (as compared to Dm) as an anticancer drug in transplantable animal tumors. Physicochemical studies of DNA structure will be undertaken to evaluate the effects of Am and Dm in P- 288 lymphocytic leukemia and in normal tissues in animals. Other drugs that also bind to DNA will be compared. The second phase proposes to define the differential sensitivity of lymphoid tissues to Am and Dm and to relate this to their clinical application alone and in combination with other antineoplastic drugs.